This research proposes to apply a novel imaging technology, high fidelity cystoscopic optical coherence tomography (OCT), to image micro-morphology of urinary bladder and to detect urothelial abnormalities (e.g. tumors). Advanced imaging techniques (e.g., fiber-optic Mach Zehnder interferometry, confocal microscopy, polarization detection and electrooptic scanning) will be used, thus allowing imaging diagnosis of bladder lesions in vivo, noinvasively, immediately and at high fidelity. Rat bladder will be imaged ex vivo and compared with histological evaluation to systematically analyze the morphological and physiological changes occurring during the methyl nitrosourea (MNU) induced tumor formation. Porcine bladder will be imaged ex vivo to compare mammalian bladders; normal procine bladder and cat bladder with iterstitial cystitis will be imaged in vivo to test the development of a cystoscopic OCT system. Most bladder cancers (e.g., carcinoma in situ) are treatable (if not curable), if diagnosed prior to metastasis and treated appropriately. Endoscopic visual inspection of surface lesions is presently the clinical standard, and conclusive diagnosis and staging of malignancy relies on surgical biopsy and histological examination. This results in an enormous number of negative biopsies of benign bladder lesions with their attendant risks and complications. Therefore, a noninvasive imaging technique is needed that allows early ultrasound and convential endoscopy, are inadequate, either because of poor resolution and limited penetration or technical imperfection. OCT, a new technology, allows noninvasive visualization of vertical cross-sectional micro-morphology (10 mum resolution) at depths of 1-3 mm beneath the bladder surface. Our preliminary results have clearly demonstrated the potential value to provide clinicians with rapid, noninvasive diagnosis of abnormalities. No other technique offers this potential at present.